Article

Identification, Cloning, Expression, and Characterization of the Gene for Plasmodium knowlesi Surface Protein Containing an Altered Thrombospondin Repeat Domain

Virginia Polytechnic Institute and State University, Блэксбург, Virginia, United States
Infection and Immunity (Impact Factor: 3.73). 10/2005; 73(9):5402-9. DOI: 10.1128/IAI.73.9.5402-5409.2005
Source: PubMed

ABSTRACT

Proteins present on the surface of malaria parasites that participate in the process of invasion and adhesion to host cells
are considered attractive vaccine targets. Aided by the availability of the partially completed genome sequence of the simian
malaria parasite Plasmodium knowlesi, we have identified a 786-bp DNA sequence that encodes a 262-amino-acid-long protein, containing an altered version of the
thrombospondin type I repeat domain (SPATR). Thrombospondin type 1 repeat domains participate in biologically diverse functions,
such as cell attachment, mobility, proliferation, and extracellular protease activities. The SPATR from P. knowlesi (PkSPATR) shares 61% and 58% sequence identity with its Plasmodium falciparum and Plasmodium yoelii orthologs, respectively. By immunofluorescence analysis, we determined that PkSPATR is a multistage antigen that is expressed
on the surface of P. knowlesi sporozoite and erythrocytic stage parasites. Recombinant PkSPATR produced in Escherichia coli binds to a human hepatoma cell line, HepG2, suggesting that PkSPATR is a parasite ligand that could be involved in sporozoite
invasion of liver cells. Furthermore, recombinant PkSPATR reacted with pooled sera from P. knowlesi-infected rhesus monkeys, indicating that native PkSPATR is immunogenic during infection. Further efficacy evaluation studies
in the P. knowlesi-rhesus monkey sporozoite challenge model will help to decide whether the SPATR molecule should be developed as a vaccine
against human malarias.

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    • "In fact, it was previously demonstrated that recombinant SPATR from Plasmodium falciparum and its orthologue in P. knowlesi were able to bind to HepG2 cells with high specificity, and antibodies generated against SPATR could inhibit P. falciparum sporozoite invasion into liver cells [6,7]. The P. falciparum SPATR protein was recognized by sera from naturally infected Africans but not control sera from two non-immune donors, indicating that this protein was recognized by the host immune system [6]. "
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